NK2 receptors are found in the periphery and the central nervous system. In the periphery, the NK2 receptor is mainly found in the smooth muscle of the gastrointestinal, respiratory and urinary tracts. In the central nervous system, the presence of NK2 binding sites in the rat brain has been demonstrated in the hippocampus, thalamus and the septum. The presence of NK2 binding sites in several limbic regions suggest that NK2 receptors may modulate emotional processes. Based on this expression pattern, the therapeutic potential of several selective NK2 receptor antagonists has been investigated in animal models of anxiety and depression.
Interestingly, Saredutant (SR48968), a selective and brain penetrant NK2 receptor antagonist was effective in exploration based procedures sensitive to anxiolytics such as elevated plus maze and the light/dark test in rodents. Efficacy in procedures sensitive to anti-depressants in mouse, gerbils and marmosets is also been documented for Saredutant. Currently Saredutant is in clinical development for depression (Phase III).
Together these data suggest that NK2 receptor antagonists have potential as a new class of anti-depressants and anxiolytics.
Furthermore, NK2 receptor antagonists may be used in the treatment of schizophrenia.